Controlling Drug Delivery Apparatus

ABSTRACT

A drug package comprising a plurality of drug vials containing drugs for delivery to a patient in a drug delivery device; and a data carrier including drug treatment information for use by the drug delivery apparatus.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation and claims priority under 35 U.S.C.§120 from U.S. patent application Ser. No. 09/930,582, filed Aug. 15,2001, which is a continuation-in-part and claims priority under 35U.S.C. §120 from of U.S. patent application Ser. No. 09/781,610, filedFeb. 12, 2001, which claims priority under 35 U.S.C. §119 from UnitedKingdom patent application no. GB0003197.1, filed Feb. 11, 2000 thecontents of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to the control of drug delivery apparatus, forexample such apparatus for delivering a drug to a patient's lungsthrough inhalation.

2. Description of the Related Art

A number of devices are available for delivering a drug into the lungsof a patient. A pneumatic or jet-type nebulizer is particularlyeffective in supplying an aerosolized drug for inhalation, but othertypes of nebulizer are also available, such as an ultrasonic typenebulizer in which the drug to be atomized is forced through a mesh byvibrating a piezo-electric crystal, whereupon the droplets passingthrough the mesh are entrained in the air being inhaled by the patient.The gauge of the mesh determines the size of the droplets which enterthe air stream. Alternatively, a dosimetric spacer can be used. Whenusing a spacer, the drug is introduced into a holding chamber of thespacer, either in aerosolized form, or by loading the air within theholding chamber with the drug in powered form. The patient then breathesfrom the holding chamber, thereby inhaling the drug laden air. Suchspacers are particularly effective when treating children or elderlypatients, and for use with certain drugs. The drug is normally deliveredover a number of breaths. Of course, the concentration of the drug ineach breath decreases over time as a result of dilution caused byambient air entering the holding chamber to replace the air beinginhaled by the patient, and as a result of the deposition of the drugwithin the chamber.

In each of the above devices, a patient receives a treatment over anumber of pulses or breaths. This might mean that a single treatmenttakes several minutes to deliver because of the amount of the drug whichis to be delivered, and the nature of the device which is delivering thedrug. Thus, in this specification, where a treatment is referred to,this refers to the delivery of a single dose of a drug over a number ofbreaths.

In addition, any references to the dose refer to the quantity of a drugdelivered to a patient during a treatment. In a course of treatments, apatient might be required to receive the dose of the drug twice a day inwhich case the patient is required to carry out two treatments each day.

As will be appreciated from this specification, the invention applies toall different types of drug delivery devices.

When a doctor prescribes a particular drug for treatment of a patient,the patient not only requires a supply of the drug, but also requires adrug delivery apparatus, for example a nebulizer or a dosimetric spacer.In the case of a nebulizer, the prescribed amount of drug for atreatment is placed in the nebulizer, and in most cases, the patientinhales from the nebulizer repeatedly until the prescribed amount ofdrug has been delivered. Unfortunately, this is no guarantee of thepatient receiving the required dose in his or her lungs. Most of thedrug tends to impact in the patient's airways before it reaches thelungs, and some of the drug is exhausted from the lungs on exhalation.Typically, about ten percent of the drug which is delivered by theatomizer reaches the lungs. However, there is a wide variation in theproportion of the drug which reaches the lungs of the patient since theeffectiveness of the drug delivery depends on the way in which thepatient uses the device. If the patient inhales deeply and regularly,then plenty of the drug will reach the lungs. However, for patientsexhibiting symptoms of pulmonary disease, breaths will be shallower andtreatment may be interrupted by symptoms of their disease such ascoughing. This will substantially reduce the amount of the drugdelivered to the patient such that they will not receive as much of thedrug as their doctor intends.

More recently, the applicant for this patent has put on the market anebulizer which calculates the dose of the drug which the patientreceives in his lungs. The nebulizer is supplied to the patientpre-programmed with the dose of a particular drug which the patientrequires. The patient is prescribed a particular drug, and before usethe patient will insert the drug, usually in liquid form, into thenebulizer. The patient then starts inhaling from the nebulizer and thedrug is delivered to the patient. The atomizer is arranged such that itonly delivers the drug during the first fifty percent of the inhalationphase of the patient, and the flow rate of inhalation of the patientthrough the device is measured, and from this, the dose of drug receivedby the patient can be calculated. Once the pre-programmed dose has beendelivered, the nebulizer will automatically stop atomizing the drugregardless of whether or not any drug remains within the nebulizer whichhas not been atomized. The atomizer must be reset before the next doseof the drug is delivered. This device is disclosed in Medic-AidLimited's earlier patent publication (GB-A-2316323), and we herebyincorporate the information contained therein by this reference in itsentirety.

Whilst the applicant's product has significantly improved the accuracyof drug delivery, if the patient's doctor wishes to change the dose ofthe drug delivered to the patient, or to change the prescribed drugaltogether, it is necessary to return the nebulizer for reprogramming,or to replace it with one with the correct drug and dose details. In aknown drug delivery system, the prescribed drug for each treatment issupplied in separate drug vials, each of which contains the requireddrug for a single treatment. Thus, a number of vials will normally besupplied to the patient for use one at a time over a period of,typically, one month. In that arrangement, each drug vial carries a barcode thereon such that, before each treatment, the bar code is read by abar code reader on the atomizer to identify what the drug is which is tobe delivered. However, the bar code must be attached to each vial,requiring increased manufacturing costs and also the carrying out ofregulatory approval tests to ensure that the adhesives of the label andthe dyes used will not contaminate the drug within the plastic vials orreduce the storage life of the product. Long term stability testing overtwo or three years is required.

According to another prior art arrangement, narcotic drugs are deliveredusing an atomizer for pain relief In that case, it is clearly importantto restrict access to the use of the drug delivery apparatus with thatdrug to the patient concerned. The patient is supplied with an I-buttonwhich is kept separate from the drug and the atomizer, and which must betouched against a contact surface on an atomizer in order to activate itfor a treatment. The button is merely used as a key to unlock theatomizer for a single treatment.

SUMMARY OF THE INVENTION

According to a first aspect of the invention, a drug package comprises aplurality of drug vials containing drugs for delivery to a patient in adrug delivery device; and a data carrier including drug treatmentinformation for use by the drug delivery apparatus.

The drug vials referred to here are suitable containers for holding thedrug which is to be administered. Drug vials are manufactured in anumber of different configurations, but normally must provide a secureenvironment which maintains the drug's stability and preventscontamination throughout the specified shelf life. It should normally beconvenient for the end user to open. The particular type of vial will beselected for a particular drug on its ability to meets these criteria,and taking account economies of manufacture. The ability to re-programthe drug delivery device without returning it is an advantage here. Thedevice can be re-programmed every time a drug is prescribed, ifnecessary, by a doctor changing the dose on the prescription. Also, thesame device can be used for different drugs, in which case theprogramming can be changed according to which drug is to be delivered.

Preferably, the drug treatment information includes at least one of thefollowing items of treatment information:

a. the dose of drug to be delivered;

b. the drug which is to be delivered;

c. the expiry date of the drug; and

d. the number of treatments in the package supplied with the datacarrier.

Preferably, the drug delivery apparatus is one for delivering the drugin the inhaled air stream to the lungs. The drug delivery device may bean aerosol generator which aerosolizes the drug such that it has aparticular size distribution suitable for inhalation, typically in therange of 1 to 5 microns. It is also preferred that the aerosol generatoroperates to aerosolize the drug during a particular part of theinhalation of a patient in order to maximize lung deposition of theaerosolize drug.

The data carrier is preferably in the form of a button. The data carriermay be moved to a receptive surface or region of the drug deliveryapparatus in order to transfer the details the treatment into thenebulizer. Preferably, only one data carrier is supplied in the package,and each time a vial of drug is to be delivered, the data carrier ismoved into the region of the drug delivery apparatus to transmit thetreatment information to it. The data carrier will normally onlytransmit the treatment information to the apparatus on a limited numberof occasions corresponding to the number of drug vials supplied in thepackage, or the apparatus will only allow a limited number of treatmentsto be delivered, corresponding to the number of drug vials.

Preferably, the data carrier is a radio frequency device which ispowered inductively from a radio frequency transmitted within the bodyof the drug delivery apparatus. One of the advantages of using RFdevices is that the system requires no electrical contacts between thedata carrier and the body of the drug delivery apparatus which could besubject to environmental contamination. The data carrier will generatean RF signal in return which will be superimposed on the driving RFsignal from the atomizer, and which is received and decoded by theatomizer.

In addition, it is preferred that information concerning a treatment betransmitted back to the data carrier where it is recorded. Once the packis finished, the data carrier may be mailed back to the doctor, orduring and after use of the pack, the recorded information can betransmitted electronically by telephone for analysis, so that the doctoris able to view how the treatments have taken place and whether or notthe patient has been using the drug delivery apparatus correctly.

Since the data carrier is supplied in or on the package with the vialsof drug, minimal regulatory difficulties are encountered. In addition,if a patient tries to use an unauthorized drug in the device, theatomizer will not operate. This is important since some drugs, such asDnase or A1AT, which are protein based drugs, may be damaged if they arecontaminated with other drug substances. An atomizer device should onlybe used for this one drug. In addition, if a drug formulation is notcompatible with the plastics used to manufacture the delivery apparatus,if the drug has been identified to the atomizer, it will not operate.

As a result of the use of the data carrier, each vial can contain moredrug than is expected to be used so as to allow for inefficiency in thepatient's breathing patterns caused by poor breathing technique or bybreathing affected by a patient's disease, such as in a MDI spacersystem or to pediatric patients. In addition, the use of the vialscontaining larger amounts of a drug can be manufactured for differenttreatments. The treatment information with the data carrier controls thedose of the drug delivered. Thus, a single vial size of drug can bemanufactured and sold, but the size of dose can vary widely depending onthe dose information carried by the treatment information. This resultsin economies of scale and reduces regulatory submissions.

The treatment information on the data carrier can be decided by, ormodified by a physician. The physician may be allowed to alter the doseof the drug to be delivered, or other treatment information. This wouldrequire the physician to use a secure interface in order to implementthe patient's specific prescription. The dose of drug, for example, canbe tailored to the patient for both individual treatments and thefrequency of treatments. This is particularly important in systemicapplications where the dose of drug in the blood needs to be controlledand tailored to each patient, such as pain control or pulmonaryhypertension drugs. The frequency of treatment also needs to becontrolled in pain control to prevent overdosing.

According to a further aspect of the invention, a drug deliveryapparatus includes a delivery portion for delivering a drug to apatient; an input for receipt of treatment information for eachtreatment to be administered to a patient; and a nebulizer controllerfor controlling the amount of drug delivered to a patient on the basisof the treatment information received. Preferably, the input is a radiofrequency input which receives the treatment information from a datacarrier at radio frequency. Preferably, the input is additionallyarranged to transmit completed treatment information to the data carrierfor recordal.

Preferably, the atomizer includes an authorization portion whichprevents atomization if any of the treatment information, such as theexpiry date of the drug, indicates that the drug is not suitable fordelivery.

According to a further aspect of the invention, an electronic datacarrier for use with a drug delivery apparatus comprises a memory forholding treatment information concerning the use of the drug deliveryapparatus in delivering a specified drug; and an output for transmittingtreatment information to the drug delivery apparatus. According to afurther aspect of the invention, a drug delivery system includes a drugdelivery apparatus for delivering a specified drug; and a electronicdata carrier containing treatment information relating to the specifieddrug, the data carrier including an output for transmitting treatmentinformation to the drug delivery apparatus before each treatment withthe specified drug whereby the drug delivery apparatus delivers thespecified drug in conformity with the treatment information.

According to a further aspect, a method of operating a drug deliveryapparatus comprises:

supplying a number vials of a drug for use with the drug deliveryapparatus;

supply for a data carrier including treatment information;

transmitting treatment information from the data carrier to the drugdelivery apparatus;

placing an amount of the drug in the drug delivery apparatus; and

delivering the drug in accordance with the treatment information fromthe data.

These and other objects, features, and characteristics of the presentinvention, as well as the methods of operation and functions of therelated elements of structure and the combination of parts and economiesof manufacture, will become more apparent upon consideration of thefollowing description and the appended claims with reference to theaccompanying drawings, all of which form a part of this specification,wherein like reference numerals designate corresponding parts in thevarious figures. It is to be expressly understood, however, that thedrawings are for the purpose of illustration and description only andare not intended as a definition of the limits of the invention. As usedin the specification and in the claims, the singular form of “a”, “an”,and “the” include plural referents unless the context clearly dictatesotherwise.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention will now be described withreference to the accompanying drawings by way of example only:

FIG. 1 shows an atomizer for delivery of a drug, including a receptiveregion, together with a data carrier in the form of a button;

FIG. 2 shows part of a flow diagram of operation of the nebulizer shownin FIG. 1;

FIG. 3 shows the remainder of the flow diagram shown in FIG. 2;

FIG. 4 shows suitable types of drug vials;

FIG. 5 is a flow chart showing how the drug delivery device can becontrolled to drive a prescription;

FIG. 6 is a graph showing inhalation flow profiles for a period of timeduring which treatment is delivered to a patient;

FIG. 7 is a graph showing a single breath of a patient;

FIG. 8 is a graph showing the minute volume plotted against time for apatient where respiratory failure occurs after an increase in minutevolume; and

FIG. 9 is a graph showing the I:E ratio for a patient over a period oftime.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

Referring to FIG. 1, a nebulizer 10 is shown including a body 1 and amouthpiece 2 through which a patient breathes to receive an atomizeddrug during inhalation. In addition, the nebulizer 10 includes a display3 for displaying information concerning the use of the machine and thetreatment being delivered, and an input 4 in the form of a receptiveregion in which a data carrier in the form of a button 5 may be placedin order to transmit information concerning the treatment into thedevice 10.

The nebulizer 10 delivers a drug to a patient in his or her inhaled airstream. The drug is supplied in a package (not shown) including a numberof individual containers or vials, each one for use in a separatetreatment. Enough vials are supplied for a course of treatments of,typically, one month. The package is supplied with a data carrier 5inside, or attached to the outside of the package, and the treatmentinformation contained therein relates to the delivery of the drug withinthe vials with which it is supplied.

In this case, the button 5 includes a small microchip having a memory,to which is connected an aerial. The atomizer 10 includes a radiofrequency transmitter connected to a further aerial for generating aradio frequency (RF) signal. When the button 5 is placed in the region4, the aerial within the button receives the radio frequency signal andgenerates electric power to operate the microchip. The microchip is thencaused to generate an additional RF signal through the aerial in thebutton 5 which contains treatment information. This is detected withinthe nebulizer 10, so that the nebulizer receives treatment informationfrom the button 5. In addition, the nebulizer 10 can receive anadditional RF signal by which information concerning actual treatmentsare downloaded into the button's memory so that the button 5 may storeinformation concerning actual treatments which may be read and analyzedlater.

A suitable RF system which can be used is the HiTag made by Phillips,and includes a button which includes a memory for holding data, and areader for reading information from the button, and for writing dataonto the button 5.

The body 1 of the drug delivery apparatus 10 includes a button holder 6in the form of a wall spaced from the surface of the body 1 adjacent theinput 4 to form a pouch in which the data carrier 5 will fit. In thiscase, the data carrier 5 can be left in the holder 6 for the duration ofa treatment, or even for the entire time that the package of drug is inuse. To minimize the possibility of loss of the button 5, the buttonholder 6 includes an interlock to prevent the button 5 from falling out.

Beneath the mouthpiece 2 is a medication chamber 8. The medicationchamber 8 includes a reservoir or well (not shown) into which the drugmust be poured before the drug delivery device 10 can be operated.Atomization of the drug takes place within the top part of the body 1,and a patient breathes in and out through the mouthpiece 2. On inhaling,drug-laden air is breathed into the lungs. To fill the drug deliveryapparatus 10, the mouthpiece 2 is removed, and the drug is poured intothe reservoir in the medication chamber 8. The mouthpiece 2 can then bereplaced on top of the chamber 8. In the case where the drug deliverydevice 10 is a nebulizer similar to the HaloLite, an intermediatecomponent must be removed before the drug is poured into the reservoir,and replaced afterwards. After a treatment has been completed, themedication chamber may be removed and emptied of any remaining drug, andwashed. If the patient requires treatment using two different drugs, adifferent medication chamber 8 may be used with the other drug, therebypreventing contamination which might have a detrimental effect on thedrugs being used.

In an alternative embodiment, the medication chamber carries the pouchwhich retains the data carrier 5. The button holder will hold the buttonover the input region 4. The advantage of this arrangement is that,where a patient has one device, but takes different medications fromdifferent medication chambers, the button is automatically changed withthe chamber. Different chambers may be required, not only when the drugsare not compatible, but also if different aerosol characteristics arerequired.

The body includes an air supply line 7, since the nebulizer 10 ispneumatic, and requires a supply of pressure air to drive atomization.

In addition to the body including the drug delivery portion towards thetop, beneath the mouthpiece 2, and one half of the radio frequencysystem, various other parts are contained therein. Although not shown inFIG. 1, there is various electronic circuitry and the like which sensesand analyses the treatments which are given, and carry out otherfunctions as are required below.

Referring to FIGS. 2 and 3, a flow diagram is shown which indicates theoperation of the drug delivery apparatus 10, and its operation inconnection with the data carrier 5. Starting at the top of FIG. 2, thelogic operations of the drug delivery device 110, which in this case isa pneumatic jet nebulizer starts at 101. A suitable pneumatic nebulizerwhich can be used is the HaloLite made by Medic-Aid. First, the question102 is asked whether or not compressed air is being received by thedevice via air supply line 7. Since it is a pneumatic nebulizer theatomization is generated by compressed air. It cannot operate until asupply of compressed air is received for example, from a pump. Once apressure detector within the apparatus detects that compressed air isreceived, the device checks the battery to ensure that sufficient poweris supplied to the device. The battery level is detected by a batterycharge detector, and is indicated to the patient on the display 3 (seeFIG. 1). The next step 104 is the calibration of an airflow sensorwithin the nebulizer. The operation of this drug delivery devicerequires that the air flow through the device generated by the breathingof a patient is known, firstly to indicate when a patient starts toinhale whereby the drug may be delivered, and secondly to calculate thedose delivered since the dose delivered is dependent on the rate ofairflow through the device.

Calibration takes place automatically, but if calibration fails, thatfailure is indicated to the patient and the device is switched offshortly thereafter. The next step, 105 is the entry into the drugdelivery device of treatment information. The patient is given a periodof thirty seconds in which to enter the treatment information by placingthe data carrier 5 in the region of a data reader 4 so that thetreatment information may be downloaded. In most instances, the datacarrier 5 is left in the pouch between treatments, and only needs to bereplaced when a new package of a drug is used. Once the treatmentinformation is downloaded, the drug delivery apparatus checks that ithas not already delivered all of the supplied doses of that drug.Provided that there are sufficient doses left, then drug delivery canbegin. If the number of doses of the drug within the package falls belowa certain proportion of the total doses originally supplied, in thiscase where 75% of the dosages have already been delivered, the patientis prompted to order a new supply, for example by telephone. In thisregard, a flashing telephone symbol appears on the display three forfive seconds. For example, if the package is supplied with twenty vials,the telephone symbol will flash each time the user seeks to use the lastfive of the vials. Alternatively, if the nebulizer is arranged to beconnected to a telephone line, a request for a new prescription can bepassed to a remote computer which will arrange for a new prescription tobe issued. Alternatively, a new package of the drug may be delivereddirectly by mail from the pharmacy on the basis of the request for a newpackage.

The data carrier 5 contains treatment information of various types,including the number of vials of a drug which was supplied in thepackage, which corresponds to the number of treatments which can beobtained from that course of treatment. The data carrier is,effectively, a memory device in which, amongst other things, the totalnumber of treatments in the course of treatments is stored. As eachtreatment is used, those treatments are counted as part of the analysisof the treatment which takes place, and re-ordering can take placeautomatically, if for example, a modem is included in the drug deliveryapparatus which will connect to the telephone system and will send out arequest for another course of treatment to be prescribed. The electronicprocessor within the drug delivery device monitors and analyses a numberof aspects of the treatment, including the number of treatments whichhave taken place. When more of the drug is required, it can be arrangedto send a signal to the part of the processing system which orders arepeat prescription via the modem. Alternatively, some other electronicform of communication can be used, such as an electronic network.

Referring to FIG. 3, which is a continuation of the flow diagram of FIG.2, the presence of compressed air is again checked at 106, and providedthat it is present, the nebulizer will wait for the patient to startinhaling. Provided that the patient inhales strongly enough, the firstthree breaths are measured using a suitable sensor, such as a pressuresensor to identify the average duration of inhalation, and the drug isthen delivered into a subsequent breath for the first 50% of thatbreath, calculated by averaging the duration of the previous threeinhalations. During treatment, the dose delivered by the drug deliveryapparatus is continually calculated. Once the total dose reaches thatwhich the patient is supposed to receive, which is included in thetreatment information supplied by the data carrier 5, an audible soundis generated, and the device is switched off. In addition, informationconcerning the treatment which has been carried out can be downloaded onto the data carrier after the treatment, or before the next treatment isstarted. Such downloaded information might include data on whentreatments are given, how long a treatment took to complete, whethertreatment was completed or not, the duration of a patient's inhalationsduring treatment, the flow rate of a patient's inhalations and the like.Other important data can also be collected. How much of the followingdata will be collected depends on the amount of analysis of thetreatment which the nebulizer can carry out. Most of the data is datawhich is either collected by existing nebulizes or is collected by otherdevices in the medical field. For example, most of the information canbe collected using the known Halolite light nebulizer and stored on thedata carrier. Firstly, the identification of the drug being used by thenebulizer is made, and the identification of the dose delivered duringeach treatment, the concentration, the volume, and the output rate ofthe nebulizer. The total duration of treatment can be stored on the datacarrier, and in the event that treatment paused for a time, that pausetime will be recorded. The total time during which the patient inhales,and the total time during which he exhales can be stored. Reference tohow this data can be used is explained later in this specification.Furthermore, on completion of delivery of a dose, the drug deliveryapparatus decrements the number of treatments left to be supplied by thepackage of drug associated with that data carrier 5.

The data carrier 5 includes a number of data fields which are programmedinto the carrier before it is inserted into a package of drug. Theseinclude the number of treatments which can be derived from that drugpackage, a security code or access code whereby the security code of thedata carrier 5 identifies to the drug delivery apparatus so that it mayonly be used to deliver one set of treatments corresponding to thepackage of drug with which it is supplied. Fields may be included in thedata carrier which can be programmed by the physician to include patientspecific parameters. In fact, the treatment information included in thefields of the data carrier could be modified by a physician in order tomake the prescription specific to that patient. This may allow the doseof the drug to be tailored to the patient's requirements, both forindividual treatments, and the frequency of treatments. This isimportant in systemic applications where the dose of drug in the bloodneeds to be controlled and tailored to each patient, such as paincontrol or pulmonary hypertension. The frequency of treatment also needsto be controlled in pain control to prevent overdosing. The data carrieralso includes a drug identification, the dose to be administered in eachtreatment, and the expiry date of the drugs. In addition, if the datacarrier is used to record the delivery of treatments, spare fields canbe made available for recording that information. The drug deliveryapparatus can download information on to the data carrier, including theserial number of the drug delivery apparatus in order to identify themachine and the patient, the number of treatments used, and otherinformation concerning the treatments. The information concerning thedelivery of treatments can then be delivered to the physician who cananalyze the treatments to ensure that they are satisfactory. Thephysician can intervene in the treatment if it is seen that there issome problem. For example, the physician will be able to tell if thepatient is not complying with the treatments, or if the patient has notadapted to that particular type of treatment. The patient might be givenadditional training in the use of the drug delivery system, or differenttreatments might be deemed to be more suitable for that patient. One ofthe particular advantages of the physician receiving the informationconcerning the treatments is that real information concerning thetreatments is received by the physician rather than the patient's viewof treatment, which can differ significantly. The information concerningthe treatments which is downloaded onto the data carrier 5 can beaccessed by the physician in several ways. For example, the patient cangive the data carrier to the physician if the physician has theappropriate apparatus for reading the information carried on the datacarrier, or can be mailed to the manufacturer of the data carrier orsome other intermediary who will download the information from the datacarrier and transfer the information to the physician. Alternatively,the information can be transferred by telephone from the patientdirectly to the physician or to some intermediary.

A telephone interface can be supplied whereby the information concerningthe delivery of treatments, patient compliance and the like are passeddown a telephone line to the manufacturer, the patient's doctor or otherintermediary. The information would typically identify the type of drugdelivery apparatus, its serial number, the drug identification, thenumber of treatments of drug used, and any other useful information. Thetelephone interface can be arranged to receive information concerningtreatments which have been carried out either directly from the drugdelivery apparatus or from the data carrier 5. If the information ispassed directly from the drug delivery apparatus, it would typically beconnected to the telephone interface by a simple data cable connection,but if the telephone interface receives the treatment information fromthe data carrier 5, it will need to include a reader to download theinformation from the data carrier. Such a reader would be technicallysimilar to the radio frequency transmitter of the atomizer, describedabove. The treatment information can then be transferred down thetelephone line either directly to the physician, or via an intermediarywhich might be a database administered by an intermediary. The databasemight be accessed directly by telephone, or via the internet. Eitherway, the patient's physician will have access to the informationconcerning the treatments which have been delivered, and will be able totake any necessary action as a result. For example, if it is clear thatthe patient is not complying with the treatments prescribed, or isunable to operate the apparatus properly, the physician may intervene bycontacting the patient. The physician will want to find out why thepatient is not complying with the treatment. The patient might turn outto be unsuitable for that treatment, or to require a different dose, ora different drug. Alternatively, the patient may just require moretraining or guidance on the proper use of the nebulizer. In addition,reference is made above to the drug delivery apparatus identifying whenonly a certain proportion of the vials in the drug package remain andindicating to the patient that more must be ordered. The use of thetelephone interface will allow the information concerning the treatmentswhich have been received by the patient to include an indicator that arepeat prescription is required. This can then be passed down thetelephone line to the intermediary or to the physician whereby a newprescription can be prepared and forwarded to the patient, or a new drugpackage of vials containing the drug can be sent directly to thepatient.

The use of the data carrier 5 in this way has a number of differentadvantages. Firstly, it can prevent the use of unauthorized drugs inthat drug delivery apparatus. This is advantageous for two reasons.Firstly, protein based drugs as rhDNase or A1AT may be damaged if theyare contaminated with other drug substances. Therefore, any drugdelivery apparatus delivering one of these drugs should only be used forthat one drug, and no other. In addition, the dose programmed into thedrug delivery apparatus for a different drug may not be appropriate forall drug substances. Thus, the chance of the wrong dose being deliveredto the patient is minimized. Also, some drugs may not be compatible withthe drug delivery apparatus concerned, for example with the plasticsused to manufacture the device.

In addition, rather than the amount of drug delivered being controlledby the nominal volume of drug in the vial all of which would often bedelivered, the amount delivered is controlled by the dose treatmentinformation in the data carrier. This is important since it allows moredrug to be included in the vial than is normally needed to take accountof inefficiency in the patient's breathing patents, but delivery willstop once the correct dose is calculated to have been delivered, beforeall of the drug in the vial has been atomized. It also means thatdifferent drug doses can be prescribed to the patient using thetreatment information in the data carrier, but that one vialconcentration and volume can be manufactured and sold for all of thesedifferent doses, thus optimizing economies of scale and reducingregulatory submissions. In the past, it would have been necessary tosupply different concentrations or different volumes of a drug dependingon the amount prescribed. The use of the data carrier 5 means that fewervolumes and concentrations of a drug need to be manufactured.

The data carrier 5 is also able to record information concerning patientcompliance with his regimen, and can even drive a direct prescription. Adoctor can be confident in the information received from the drugdelivery apparatus 10 which is recorded on the data carrier 5. Thedoctor does not need to rely on the patient's own reports of compliancenor their inhalation efficiency.

Since the data carrier 5 is supplied with a number of vials of a drug,different styles of packs can be used for different therapeuticapplications. Some drugs must be supplied in a plastic unit dose vial,and others must be supplied in two-part packages for reconstitution atthe point of use. Both of these drug vials can be accommodated becausethe data carrier is attached to the outside of the box, and contains thedosing information for the whole pack of the drug, typically one month.It is not attached to individual drug vials, and minimizes thepackaging, regulatory and development requirements for integrating thedrugs into the drug delivery system. It avoids potential contaminationproblems on drug packs, which is a significant issue where labels orprinting are applied to plastic vials and lengthy stability tests arerequired to ensure there is no leaking of dyes or adhesives into thedrug over the storage life of the product, which may be up to two years.

FIGS. 4 a to 4 f show a number of different types of vials which shouldbe suitable for use in carrying out this invention. FIG. 4 a is a dualcompartment vial for holding two different components apart until thedrug is ready to be dispensed. The two substances can then be mixedimmediately prior to use. For example, one compartment might contain aliquid and the other a powder which when mixed together dissolves thepowder into the liquid or both compartments could contain liquids whichare mixed into the substance to be delivered. Such packages aregenerally known in this field, and often involve the rotation of theplunger in order to break the seal between the two compartments.

The vial in FIG. 4 b is a glass vial with an elastomeric stopper. It isdesigned to hold liquids or powders.

FIG. 4 c shows a glass vial for containing liquid. The top of the vialis snapped off to allow access to the liquid.

FIG. 4 d shows a gelatine capsule for holding powders for inhalation.The gelatine capsule must be broken in order to gain access to thepowder.

FIG. 4 e shows a foil blister pack for holding powdered drug.

FIG. 4 f shows a polyethylene blow fill seal vial for holding a liquiddrug.

Of course, vials are not limited to these examples, which are entirelyillustrative of vials generally.

The drug may also be packaged in part of the aerosol generation system,as opposed to a separate vial, such as in the nebulizer chamber, ormedication chamber. This is a benefit to the patient from ease of use,since the drug dose does not have to be transferred to the chamber inorder for treatment to take place, and the chamber is disposed of afterthe treatment, avoiding the need for cleaning and the potential forcontamination. In this case, the medication chamber or the like actuallyconstitutes a vial suitable for holding and transporting the drug.

It should be understood that the embodiment described above is anexample of the invention, and that this patent is not limited to it. Forexample, other drug delivery apparatus can be used, and other types ofnebulizers, such as piezo-electric and ultrasonic nebulizers or powderdelivery systems such as a dosimetric spacer. Also, the data carriercould be one which requires electrical contact to take place in order totransfer data, such as an I-button.

FIG. 5 is a flow diagram showing how the data collected by the drugdelivery device can be returned to a data centre for analysis. The datacentre could be located at the local hospital or clinic, but is mostlikely to be centralized with the results of the processing being sentto the clinician responsible for the patient. Initially, the doctor willprescribe some medication and agree a protocol for treatment with thepatient. This will be used to initiate the supply of the product to thepatient and set the processing by the data centre. Each time the patientreturns information via the data carrier or via a communications link,analysis takes place, and if everything is proceeding satisfactorily,more medication is supplied to the patient, but if there is somethingwhich seems unsatisfactory in the data, the doctor is contacted todiscuss the treatment with the patient.

In FIG. 5, The drug delivery device 50, in this case a Halolite made byMedic-Aid Limited, is used by the patient, and from time to time a modem51 is used to pass treatment information back to the data centre 52,either directly or by placing the data carrier 53 in the modem.Alternatively, the data carrier 53 is posted to the data centre 52. Thedata is analyzed at step 54, and if the result is satisfactory, moredrug is supplied, either by the issue of a prescription, or by thedirect dispensing of more of the drug. If the result is notsatisfactory, the doctor is contacted, and he or she can contact thepatient to identify problems.

It was explained above that the amount of information concerningtreatments which take place that can be put on the data carrier dependson the sophistication of the nebulizer, and it's ability to capturetreatment information. Using the Halolite nebulizer, a great deal ofinformation can be collected and placed on the data carrier. This caninclude an identification of the drug, the dose of drug delivered duringeach treatment, the total number of pulses required to deliver the dose,the total treatment time, the total inhalation time, the totalexhalation time and the peak inhalation flow. If a patient pausestreatment, then the pause time can also be recorded and stored on thedata carrier. The drug identification identifies not only the type ofdrug which is delivered, but the concentration of the drug composition,and the dose which should be delivered. The output rate of the nebulizermay also be relevant. The total treatment time is the total duration oftreatment from the beginning to end. The total inhalation time may becalculated as the total time from start to end of treatment where theflow is greater than zero where the pressure within the nebulizer isless than the ambient pressure. Similarly, the total exhalation time isthe total time from the start of exhalation to the end of exhalationwhere the flow is negative and the pressure within the nebulizer isgreater than the ambient pressure.

FIGS. 6 and 7 are graphs showing the flow of air against time. In FIG.6, the flow is indicated for three breaths 61 before the treatmentstarts 62 where marked with an arrow. During the first breath, the firsthalf of the inhalation phase is indicated with hatching to denote theperiod of time 63 in which the nebulizer is delivering the drug into theinhaled stream of air. Similar patterns occur on subsequent inhalations.On occasions, short breaks in the inhalation flow of the patient occursuch as at 64, which are not counted as deliberate pauses since they areshort, and which might occur as a result of the patient suffering fromdisease symptoms, for example exhibited by coughing. However, over thewhole treatment these may add up to a significant proportion of thetreatment time. If the patient needs to pause the treatmentdeliberately, for example to answer the telephone, and since theHalolite is pneumatically driven, the compressor generating the flow ofair driving the atomizer will be switched off, and that period is whichthe compressor is switched off in this case corresponds to the pausedperiod. Eventually, once the required dose of the drug has beendelivered, in this case after 12 pulses of the drug, the treatmentfinishes at 66.

In FIG. 7, a single breath cycle with various characteristics of thebreath shown, including peak inhalation flow, the duration of the pulseduring which the drug is delivered, the duration of inhalation, theduration of exhalation, and the peak exhalation flow.

Once all of this information has been downloaded onto the data carrier,the data can be downloaded for analysis. Wherever this analysis takesplace, quite a lot of information can be calculated about the patientstreatment. For example, the mean inhalation time can be calculated bydividing the total inhalation time by the total number of pulses, theinhalation to exhalation ratio can be obtained by dividing the totalinhalation time by the total exhalation time. The total time duringwhich no flow occurs can be derived by taking the total treatment timeand subtracting from that the total inhalation and exhalation timetogether with any pause. The number of breaths per minute can becalculated, as can the mean tidal volume, the latter of which can becalculated by multiplying the mean inhalation flow by the meaninhalation time by 0.7 and then dividing by 60, as defined in FIG. 5 ofPCT/GB99/03540. The mean tidal volume for exhalation can be calculatedin a similar way, but by using the mean exhalation flow and the meanexhalation time instead. The minute volume can be calculated bymultiplying the number of breaths per minute by the mean tidal volume.The mean pulse time be calculated, as can the mean pulse percentage overthe duration of the inhalation time. These calculations could beperformed prior to saving the information on the data carrier.

By monitoring these parameters, it will be possible to see if thepatient is using the device effectively. The data will show that theyare keeping the mouthpiece in their mouth if the total no-flow time islow. If they are breathing consistently in and out through their mouth,the inhalation and exhalation volumes will be matched and theirinhalation to exhalation ratio should be within the normal range. Themean pulse time will show that the patient's inhalation tidal volume andinhalation time are sufficient to achieve the maximum pulse length.During treatment the following four criteria should be met:

1. The total no flow time is less than 10% of the total treatment timeless pause time.

2. The inhalation to exhalation ratio should be within the range of 1:1to 1:2.

3. The mean pulse percentage should be approximately 80%.

4. The mean tidal inhalation of volume should be very similar to themean tidal exhalation volume.

If any of these characteristics are not met it may be necessary for thepatient's clinician to take action.

The patient's physical condition can be assessed from the data, with thedata trended overtime in order to see the changes in the patient'scondition. Trending these parameters over time allows trends which areindicative of the patient's underline condition to be observed, such asthe minute volume in FIG. 8. As a patient's lung condition deteriorates,the minute volume is increased to compensate for poor lung ventilation.Minute volume can be increased until the work of breathing is too greatto be sustained and the patient goes into respiratory failure. Thistypically results in admission to accident and emergency or tosupplementary oxygen being required. In FIG. 8, the trend of a patientwith respiratory failure is shown. If the no flow time or the inhalationto exhalation ratio are increasing over subsequent treatments, this mayindicate a worsening of the patient's condition, for example as a resultof increased coughing, as shown in FIG. 9.

Of particular use for trending over time are the following:

-   -   1. The inhalation to exhalation ratio.    -   2. Mean tidal volume.    -   3. The percentage pulse.    -   4. Minute volume.

Again if a clinician sees that a patient's condition is deteriorating onthe basis of the trending of the parameters, he can take action with thepatient.

Thus, there are two particular uses to collecting and analyzing thiskind of data, firstly, to assess now well a patient is complying withthe treatment and allow the clinician to take action to optimize thetreatment and secondly, to allow long term trends in a patient'scondition to be assessed.

The benefits of analyzing the breathing parameters can also be obtainedwithout the data carrier by saving the data in an alternative memorywithin the delivery system and the data could also be analyzed byonboard algorithms to advise the patient of a change in his condition.

Although the invention has been described in detail for the purpose ofillustration based on what is currently considered to be the mostpractical and preferred embodiments, it is to be understood that suchdetail is solely for that purpose and that the invention is not limitedto the disclosed embodiments, but, on the contrary, is intended to covermodifications and equivalent arrangements that are within the spirit andscope of the appended claims. For example, it is to be understood thatthe present invention contemplates that, to the extent possible, one ormore features of any embodiment can be combined with one or morefeatures of any other embodiment.

1. A system for delivery of a drug to a patient comprising: a drug delivery device arranged to deliver a predetermined dose of the drug to the patient over a plurality of breaths, wherein the predetermined dose is delivered during a single compliant treatment, the device including a breath analyzer which (i) analyzes a patient's breathing during drug delivery, wherein the analysis by the breath analyzer includes quantitatively measuring at least one parameter of the patient's breathing; and (ii) generates breath information on a patient's breathing during drug delivery wherein the breath information includes the at least one quantitative measurement of the patient's breathing; a data carrier onto which the drug delivery device is arranged to place the breath information for each treatment; and a data analyzer arranged to analyze the breath information from the data carrier, and to derive characteristics of the patient's breathing; and a trend generator for analyzing the breath information and the characteristics of the patient's breathing over multiple treatments.
 2. A system according to claim 1, wherein the data analyzer includes means for identifying non-compliant use of the drug delivery device.
 3. The system for delivery of a drug to a patient according to claim 1, wherein the breath information includes inhalation time and a total number of pulses, and wherein the data analyzer calculates a mean inhalation time value by dividing the total inhalation time by the total number of pulses.
 4. The system for delivery of a drug to a patient according to claim 1, wherein the breath information includes inhalation time and exhalation time and wherein the data analyzer calculates an inhalation to exhalation ratio value by dividing the total inhalation time by the total exhalation time.
 5. A method of identifying changes in condition of a patient comprising: delivering a predetermined dose of medication over a plurality of breaths, wherein each predetermined dose is delivered during a single compliant treatment; analyzing a patient's breathing during drug delivery, including quantitatively measuring at least one parameter of that breathing; generating breath information from the patient's breathing during drug delivery, including the quantitative measurement of that breathing; transferring the breath information to a data analyzer; deriving characteristics from the breath information; and analyzing the characteristics over a number of treatments to identify trends in those characteristics.
 6. The method according to claim 5, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and measuring a total number of pulses, and wherein the step of deriving characteristics of the patient's breathing includes calculating a mean inhalation time value by dividing the total inhalation time by the total number of pulses.
 7. The method according to claim 5, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and an exhalation time, and wherein the step of deriving characteristics of the patient's breathing includes calculating an inhalation to exhalation ratio value by dividing the total inhalation time by the total exhalation time.
 8. The method according to claim 5, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and a total number of pulses, and wherein the step of deriving characteristics includes calculating a mean inhalation time value by dividing the total inhalation time by the total number of pulses.
 9. A system for delivery of a drug to a patient comprising: a drug delivery device arranged to deliver a predetermined dose of the drug to the patient over a plurality of breaths, the drug delivery device including a wireless transceiver, wherein the predetermined dose is delivered during a single compliant treatment, the device including a breath analyzer which (i) analyses a patient's breathing during drug delivery, wherein the analysis by the breath analyzer includes quantitatively measuring at least one parameter of the patient's breathing; and (ii) generates breath information on a patient's breathing during drug delivery wherein the breath information includes the at least one quantitative measurement of the patient's breathing; a data carrier onto which the drug delivery device is arranged to place the breath information for each treatment, the data carrier including a wireless transceiver for wireless communication with the drug delivery transceiver; and a data analyzer arranged to analyze the breath information from the data carrier, and to derive characteristics of the patient's breathing; and a trend generator for analyzing the breath information and the characteristics of the patient's breathing over multiple treatments.
 10. A system according to claim 9, wherein the data analyzer includes means for identifying non-compliant use of the drug delivery device.
 11. The system for delivery of a drug to a patient according to claim 9, wherein the breath information includes inhalation time and a total number of pulses, and wherein the data analyzer calculates a mean inhalation time value by dividing the total inhalation time by the total number of pulses.
 12. The system for delivery of a drug to a patient according to claim 9, wherein the breath information includes inhalation time and exhalation time and wherein the data analyzer calculates an inhalation to exhalation ratio value by dividing the total inhalation time by the total exhalation time.
 13. A method of identifying changes in condition of a patient comprising: delivering a predetermined dose of medication over a plurality of breaths, wherein each predetermined dose is delivered during a single compliant treatment; analyzing a patient's breathing during drug delivery, including quantitatively measuring at least one parameter of that breathing; generating breath information from the patient's breathing during drug delivery, including the quantitative measurement of that breathing; wirelessly transferring the breath information to a data analyzer; deriving characteristics from the breath information; and analyzing the characteristics over a number of treatments to identify trends in those characteristics.
 14. The method according to claim 13, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and measuring a total number of pulses, and wherein the step of deriving characteristics of the patient's breathing includes calculating a mean inhalation time value by dividing the total inhalation time by the total number of pulses.
 15. The method according to claim 13, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and an exhalation time, and wherein the step of deriving characteristics of the patient's breathing includes calculating an inhalation to exhalation ratio value by dividing the total inhalation time by the total exhalation time.
 16. The method according to claim 13, wherein the step of quantitatively measuring at least one parameter includes measuring an inhalation time and a total number of pulses, and wherein the step of deriving characteristics includes calculating a mean inhalation time value by dividing the total inhalation time by the total number of pulses. 